BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) placement is a common treatment for idiopathic normal pressure hydrocephalus (iNPH), but patients may require VPS revision. This study aims to evaluate the effectiveness of a standardized VPS placement protocol by comparing indications and rates of shunt revision compared with a historical institutional cohort. METHODS: All patients treated with VPS for “suspected” iNPH at a tertiary care center between January 2000 and January 2023 were retrospectively reviewed and divided into temporally distinct historical (before 2017) and standardized (after 2017) cohorts. Cumulative incidence and timing of VPS revision were compared using competing risks analyses. RESULTS: A total of 561 patients (median age 75.0 years) were identified with 324 (57.8%) in the historical and 237 (42.2%) in the standardized cohorts. Significant variations in surgical technique and shunt hardware were noted between the cohorts. With a median follow-up of 11.4 months for historical and 12.4 months for standardized cohort, shunt revisions occurred in 19.4% and 8.4% of patients in the historical and standardized cohorts, respectively ( P < .001). Revision indications also varied significantly with lower rates of overdrainage ( P < .001), infection ( P < .001), and proximal malfunction ( P = .042) but higher rate of distal malfunction ( P = .03) in the standardized cohort. Notably, no infections were noted in the standardized cohort. CONCLUSION: Risk of shunt revision among iNPH patients may be associated with modifiable factors related to surgical technique and shunt hardware selection. Importantly, no short-term complications such as hemorrhage, infection, or catheter malposition were observed with the standardized protocol. Development and refinement of standardized shunt protocols for iNPH patients should be commonplace to facilitate tracking, identification, and modification of modifiable technical risk factors.
3D Osteoimmune Stem Cell Spheroids with Osteoinduction and Immunomodulation Dual Functionality for
In Vivo
Bone Tissue Engineering
Study Design Retrospective cohort analysis. Objective (1) Develop a novel computed tomography (CT)-based assessment of endplate bone density (EP-HU), (2) Determine if EP-HU was a stronger predictor than trabecular HU for subsidence after transforaminal lumbar interbody fusion (TLIF). Methods All adult patients who underwent single-level TLIF for lumbar degenerative conditions at an academic center between 2017-2022 were retrospectively identified. EP-HU was calculated from a 2 mm superior and inferior endplate region on the preoperative mid sagittal CT scans, accounting for surface undulations. Lumbar vertebral HUs (trabecular region) were determined in a standard fashion on axial CT. EP-HU + vertebral HU served as an aggregate bone quality metric. Interbody subsidence (≥2 mm threshold) was directly measured on the endplate-facing surface of 1 year CT scans. Univariate and multivariate analysis compared subsidence based on CT bone metrics. Results A total of 114 patients met the inclusion/exclusion criteria. There was no significant difference in fusion or reoperation rate based on subsidence occurrence. Both vertebral HU ( P = .012) and EP-HU ( P < .001) were associated with subsidence. In receiver operating curves, EP-HU was more optimal for subsidence prediction than vertebral HU, but the aggregate metric further optimized the specificity and total area under the curve. In a predictive logistic regression model EP-HU + vertebral HU (aggregate HU < 515 odds ratio: 7.82, P < .001) was a strong independent predictor of subsidence. Conclusion Preoperative calculation of EP-HUs in addition to vertebral HUs may enhance prediction of TLIF subsidence where aggregate endplate and vertebral HU < 515 can be used to identify high risk patients.
Bone Enzyme-Responsive Biodegradable Poly(propylene fumarate) and Polycaprolactone Polyphosphoester Dendrimer Cross-Linked via Click Chemistry for Bone Tissue Engineering
AbstractThe growing aging population, with its associated chronic diseases, underscores the urgency for effective tissue regeneration strategies. Biomaterials play a pivotal role in the realm of tissue reconstruction and regeneration, with a distinct shift toward minimally invasive (MI) treatments. This transition, fueled by engineered biomaterials, steers away from invasive surgical procedures to embrace approaches offering reduced trauma, accelerated recovery, and cost‐effectiveness. In the realm of MI tissue repair and cargo delivery, various techniques are explored. While in situ polymerization is prominent, it is not without its challenges. This narrative review explores diverse biomaterials, fabrication methods, and biofunctionalization for injectable pre‐formed scaffolds, focusing on their unique advantages. The injectable pre‐formed scaffolds, exhibiting compressibility, controlled injection, and maintained mechanical integrity, emerge as promising alternative solutions to in situ polymerization challenges. The conclusion of this review emphasizes the importance of interdisciplinary design facilitated by synergizing fields of materials science, advanced 3D biomanufacturing, mechanobiological studies, and innovative approaches for effective MI tissue regeneration.
Injectable bioactive poly(propylene fumarate) and polycaprolactone based click chemistry bone cement for spinal fusion in rabbits
AbstractDegenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano‐hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano‐hydroxyapatite (nHA) and the released rhBMP‐2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.
Biodegradable poly(caprolactone fumarate) 3D printed scaffolds for segmental bone defects within the Masquelet technique
Abstract Segmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one‐stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4‐week implantation study. Histological analysis, including tissue staining and immunohistochemistry with bone‐specific antibodies, was conducted for histomorphometry evaluation. The PCLF/PCL spacers demonstrated compressive properties within 6 ± 0.5 MPa (strength) and 140 ± 15 MPa (modulus). Both porous PCLF/PCL and Nonporous PMMA formed collagen‐rich membranes (PCLF/PCL: 92% ± 1.3%, PMMA: 86% ± 1.5%) similar to those induced in the Masquelet technique, indicating PCLF/PCL's potential for one‐stage healing. Immunohistochemistry confirmed biomarkers for tissue regeneration, underscoring PCLF/PCL's regenerative capabilities. This research highlights PCLF/PCL scaffolds' ability to induce membrane formation in critical‐sized segmental bone defects, supporting their use in one‐stage surgery. Both solid and porous PCLF/PCL spacers showed adequate compressive properties, with the porous variants exhibiting BMP‐2 expression and woven bone formation, akin to clinical standard PMMA. Notably, the early ossification of the membrane into the pores of porous scaffolds suggests potential for bone interlocking and regeneration, potentially eliminating the need for a second surgery required for PMMA spacers. The biocompatibility and biodegradability of PCLF/PCL make them promising alternatives for treating critical bone defects, especially in vulnerable patient groups.
Bioactive Moldable Click Chemistry Polymer Cement with Nano-Hydroxyapatite and Growth Factor-Enhanced Posterolateral Spinal Fusion in a Rabbit Model